Description
- Abstract:
- Chordoma is a rare cancer of notochordal origin with frequent recurrence and limited treatment options. To better understand recurrence-associated changes and oncogenesis in chordoma, this study combined transcriptomic analysis, ErbB signaling experiments, and early 3D organoid optimization. Existing bulk RNA-seq and NanoString datasets comparing primary and recurrent chordoma were analyzed, and additional bulk RNA-seq comparing primary chordoma with disc tissue was performed. Then ErbB signaling was examined in recurrent chordoma-derived MUG-Chor1 cells using siRNA targeting ERBB2 and EGR2, followed by qPCR and Western blot. Initial organoid experiments were conducted using chordoma-derived cell lines under suspension and Matrigel-based conditions with different supplements. Bulk RNA-seq identified transcriptomic differences between primary vs recurrent chordoma, and NanoString data supported recurrence-associated changes in progression and immune programs. The progression panel highlighted altered growth and proliferation pathways, including PI3K-AKT/ErbB signaling. The immune panel showed higher expression of inflammatory and cytokine-related genes, including EGR2 in recurrent samples. Primary chordoma vs disc tissue analysis also demonstrated a distinct transcriptional profile, with stronger enrichment of stress-adaptive metaprograms in chordoma, whereas disc tissue was more enriched for fibroblast, stromal, remodeling, and matrix-related programs. In MUG-Chor1 cells, ERBB2-targeting siRNA reduced ERBB2 transcript and protein levels and decreased EGR2 transcript expression, although clear EGR2 protein reduction was not observed. PKI-166 treatment likewise reduced ERBB2 and EGR2 transcript expression, while stronger protein-level effects were observed in decreased AKT and ERK phosphorylation with reduced cell viability and proliferation. During organoid optimization, collagen-containing matrix conditions supported denser cell aggregation and growth compared with Matrigel-only conditions. Together, these findings identify recurrent chordoma as a distinct molecular state, support the ErbB axis as a plausible therapeutic target, and suggest that extracellular matrix context may influence chordoma cell behavior. The study also provides a preliminary foundation for future 3D chordoma organoid development.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Shin, Leah,
"Transcriptomic Characterization of Chordoma with Functional Investigation of ErbB Signaling and Early-Stage 3D Organoid Optimization"
(2026).
Biology and Medicine Theses and Dissertations, Biotechnology.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:uj2rj42s/
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Biology and Medicine Theses and Dissertations
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